AbstractSince 2002, three novel coronavirus outbreaks have occurred: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. A better understanding of the transmission potential of coronaviruses will result in adequate infection control precautions and an early halt of transmission within the human population.

摘要自2002年以来，发生了三起新的冠状病毒爆发：严重急性呼吸综合征冠状病毒（SARS-CoV-1），中东呼吸综合征冠状病毒（MERS-CoV）和SARS-CoV-2。更好地了解冠状病毒的传播潜力将导致适当的感染控制预防措施，并尽早停止在人群中的传播。

Experiments on the stability of coronaviruses in the environment, as well as transmission models, are thus pertinent.Here, we show that transgenic mice expressing human DPP4 can be infected with MERS-CoV via the aerosol route. Exposure to 5 × 106 TCID50 and 5 × 104 TCID50 MERS-CoV per cage via fomites resulted in transmission in 15 out of 20 and 11 out of 18 animals, respectively.

因此，冠状病毒在环境中的稳定性实验以及传播模型是相关的。在这里，我们显示表达人DPP4的转基因小鼠可以通过气溶胶途径感染MERS-CoV。通过fomites暴露于每笼5×106 TCID50和5×104 TCID50-MERS-CoV分别导致20只动物中的15只和18只动物中的11只传播。

Exposure of sentinel mice to donor mice one day post inoculation with 105 TCID50 MERS-CoV resulted in transmission in 1 out of 38 mice via direct contact and 4 out of 54 mice via airborne contact. Exposure to donor mice inoculated with 104 TCID50 MERS-CoV resulted in transmission in 0 out of 20 pairs via direct contact and 0 out of 5 pairs via the airborne route.

在接种105 TCID50-MERS-CoV后一天，将前哨小鼠暴露于供体小鼠，导致38只小鼠中有1只通过直接接触传播，54只小鼠中有4只通过空气传播。暴露于接种104 TCID50-MERS-CoV的供体小鼠导致20对中的0对通过直接接触传播，5对中的0对通过空中途径传播。

Our model shows limited transmission of MERS-CoV via the fomite, direct contact, and airborne routes. The hDPP4 mouse model will allow assessment of the ongoing evolution of MERS-CoV in the context of acquiring enhanced human-to-human transmission kinetics and will inform the development of other transmission models..

我们的模型显示，MERS-CoV通过fomite，直接接触和空气传播途径的传播有限。hDPP4小鼠模型将允许在获得增强的人与人之间传播动力学的背景下评估MERS-CoV的持续进化，并将为其他传播模型的开发提供信息。。

IntroductionIn the last two decades, three novel coronaviruses have caused outbreaks in the human population. Severe acute respiratory syndrome coronavirus (SARS-CoV-1) was first identified in 2003 after it caused human cases in the Guangdong province, China, in November 2002. From Guangdong, the virus spread to 37 countries, resulting in >8000 infected people with a case fatality rate of 9.5%1.

引言在过去的二十年中，三种新型冠状病毒已在人群中引起爆发。严重急性呼吸综合征冠状病毒（SARS-CoV-1）于2002年11月在中国广东省引起人类病例后，于2003年首次被鉴定。该病毒从广东传播到37个国家，导致8000多名感染者，病死率为9.5%1。

Middle East respiratory syndrome coronavirus (MERS-CoV) was first detected in 2012 and still circulates in the dromedary camel population, from which it infects the human population. Since 2012, more than 2600 cases with a case fatality rate of 36%2 have been reported. The largest pandemic with a coronavirus to date started in December 2019 and was caused by SARS-CoV-2.

中东呼吸综合征冠状病毒（MERS-CoV）于2012年首次被检测到，目前仍在单峰骆驼种群中传播，并感染人群。自2012年以来，已报告2600多例病例，病死率为36%2。。

To date, more than 770 million cases have been reported, resulting in nearly 7 million deaths3.A better understanding of the transmission potential of coronavirus is crucial when devising personal protection equipment for healthcare staff and quarantine measurements. The stability of MERS-CoV, SARS-CoV-1, and SARS-CoV-2 has been investigated under several different environmental conditions in both fomites and aerosols4,5,6.

迄今为止，已报告超过7.7亿例病例，导致近700万人死亡3。在为医护人员设计个人防护设备和检疫措施时，更好地了解冠状病毒的传播潜力至关重要。已经在几种不同的环境条件下，在烟雾和气溶胶中研究了MERS-CoV，SARS-CoV-1和SARS-CoV-2的稳定性4,5,6。

Experimental transmission models have been developed for SARS-CoV-2 and focus mainly on hamsters and ferrets7,8,9,10,11,12,13, whereas SARS-CoV-1 transmission has been shown in ferrets and cats13,14. However, transmission of MERS-CoV in animal models has not yet been reported.A review of 681 MERS cases in the Kingdom of Saudi Arabia (KSA) estimated that 12% of cases were infected via direct exposure to dromedary camels, and 88% resulted from human-to-human transmission15.

已经为SARS-CoV-2开发了实验传播模型，主要集中在仓鼠和雪貂7,8,9,10,11,12,13，而SARS-CoV-1传播已在雪貂和猫中显示13,14。然而，尚未报道MERS-CoV在动物模型中的传播。对沙特阿拉伯王国（KSA）681例MERS病例的回顾估计，12%的病例是通过直接接触单峰骆驼感染的，88%是由于人与人之间的传播15。

Analysis of transmission dynamics showed that the number of subsequent generations is limited. The risk of a human-to-human.

传输动力学分析表明，后代的数量是有限的。人与人之间的风险。

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Download referencesAcknowledgementsThe authors would like to thank Laura Tally and colleagues for assistance with mouse breeding, the Rocky Mountain Veterinary branch for assistance with high containment husbandry and cage design, Tina Thomas, Dan Long and Rebecca Rosenke for assistance with pathology and Anita Mora and Ryan Kissinger for assistance with the figures.

下载参考文献致谢作者要感谢劳拉·塔利（LauraTally）及其同事在小鼠繁殖方面的帮助，感谢落基山兽医分会在高遏制饲养和笼子设计方面的帮助，感谢蒂娜·托马斯（TinaThomas）、丹·朗（DanLong）和丽贝卡·罗森克（RebeccaRosenke）在病理学方面的帮助，感谢安妮塔·莫拉（AnitaMora）和瑞安·基辛格（RyanKissinger）在数字方面。

This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH).FundingOpen access funding provided by the National Institutes of Health.Author informationAuthor notesDania M. Figueroa AcostaPresent address: Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USAAuthors and AffiliationsDivision of Intramural Research, Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USANeeltje van Doremalen, Trenton Bushmaker, Robert J.

这项研究得到了美国国立卫生研究院（NIH）国家过敏与传染病研究所（NIAID）壁内研究计划的支持。基金由国立卫生研究院提供的开放获取资金。作者信息作者notesDania M.Figueroa Acostat目前的地址：美国纽约州西奈山伊坎医学院医学系传染病科作者和附属机构美国国立卫生研究院过敏与传染病研究所病毒学实验室壁内研究部，国立卫生研究院，汉密尔顿，MT，USANeeltje van Doremalen，Trenton Bushmaker，Robert J。

Fischer, Dania M. Figueroa Acosta, Rebekah J. McMinn, Michael Letko & Vincent J. MunsterPaul G. Allen School for Global Health, Washington State University, Pullman, WA, USAAtsushi OkumuraDivision of Intramural Research, Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USADana Scott & Greg SaturdayAuthorsNeeltje van DoremalenView author publicationsYou can also search for this author in.

菲舍尔（Fischer），达尼亚·M·菲格罗亚·阿科斯塔（Dania M.Figueroa Acosta），丽贝卡·J·麦克敏（Rebekah J.McMinn），迈克尔·莱特科（Michael Letko）和文森特·J·蒙斯特保罗·G·艾伦（Vincent J.MunsterPaul G.Allen）华盛顿州立大学全球健康学院（School for Global Health），华盛顿州普尔曼（Pullman），USAAtsushi OkumuraDivision of Internal Research，Rocky Mountain Veterinary Branch，National Institute of Allergy and Infectio。

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PubMed Google ScholarContributionsN.v.D. and V.J.M. wrote the main manuscript text. N.v.D., R.F., T.B., A.O., R.M., M.L., D.S., G.S., D.F.A., and V.J.M. performed the research. All authors reviewed the manuscript.Corresponding authorCorrespondence to

PubMed Google ScholarContributionsN.v.D.和v.J.M.撰写了主要的手稿文本。N、 v.D.，R.F.，T.B.，A.O.，R.M.，M.L.，D.S.，G.S.，D.F.A。和v.J.M.进行了这项研究。所有作者都审阅了手稿。对应作者对应

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Reprints and permissionsAbout this articleCite this articlevan Doremalen, N., Bushmaker, T., Fischer, R.J. et al. Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model.

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